Dual ErbB1 and ErbB2 receptor tyrosine kinase inhibition exerts synergistic effect with conventional chemotherapy in pancreatic cancer.

Abstract:

:Patient survival in pancreatic cancer remains poor with gemcitabine (GEM)-based regimens. The target specific molecular agent lapatinib, a dual ErbB1 and ErbB2 receptor tyrosine kinase inhibitor, has shown significant activity against ErbB1 and ErbB2-expressing tumors. Since pancreatic tumors frequently overexpress these proteins, we investigated its effects, both alone and in conjunction with 5-FU or GEM. The pancreatic cancer cell lines PANC-1 and AsPC were treated with varying doses of lapatinib in vitro. The effects on ErbB1/ErbB2 protein phosphorylation and on the cell survival protein survivin were determined by western blotting. Cytotoxicity was determined by MTT assay and apoptosis was measured using the caspase-3 colorimetric assay. Similar dose-response lapatinib experiments were conducted with varying concentrations of 5-FU or GEM and isobolograms were constructed to evaluate therapeutic synergy. Lapatinib inhibited protein phosphorylation in the range of 4-16 µM, a clinically achievable concentration. The lapatinib-treated cells showed a dose-dependent inhibition of cell proliferation and induction of apoptosis at the same concentrations that blocked ErbB1/ErbB2 phosphorylation. The addition of 5-FU or GEM to these cells resulted in synergistic effects. The lapatinib-treated cells also demonstrated downregulation of survivin. Simultaneous dual ErbB1 and ErbB2 receptor tyrosine kinase inhibition with lapatinib results in significant reduction of pancreatic cancer cell growth and proliferation. These effects occur at clinically achievable concentrations and are synergistic with the effects of 5-FU or GEM. These findings support the potential role of lapatinib in the treatment of pancreatic cancer.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Singla S,Pippin JA,Drebin JA

doi

10.3892/or.2012.2053

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

2211-6

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

28

pub_type

杂志文章
  • GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system.

    abstract::Prostate cancer (PCa) growth initially depends on circulating androgens. Gonadotropin-releasing hormone (GnRH) agonists are currently used for the treatment of PCa. However, after an initial responsiveness to hormonal deprivation, PCa progresses and metastasizes. Recently, also GnRH antagonists have been used for clin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.15.2.393

    authors: Dondi D,Festuccia C,Piccolella M,Bologna M,Motta M

    更新日期:2006-02-01 00:00:00

  • The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy.

    abstract::Medulloblastoma is the most common malignant tumor of the central nervous system in children. The insulin-like growth factor-I receptor (IGF-IR) is an important growth factor for medulloblastoma. The novel IGF-I receptor (IGF-IR) kinase inhibitor NVP-ADW742 has in vitro activity against tumors. Daoy cells were treated...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1233

    authors: Zhou H,Rao J,Lin J,Yin B,Sheng H,Lin F,Zhang N,Yang L

    更新日期:2011-06-01 00:00:00

  • Molecular and immunological aspects of p53 and p53-autoantibodies in head and neck squamous cell carcinoma.

    abstract::The tumour suppressor protein p53 (wild-type = wt-p53) is of major importance in the genetic integrity of the cell. Mutations of the p53-gene (mt-p53) are the most frequent genetic aberrations identified in different tumour entities. As analyzed in a wide variety of human malignomas, mt-p53 evokes a specific immune re...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000568

    authors: Cordes C,Von Lingen J,Görögh T,Ambrosch P,Gottschlich S,Hoffmann M

    更新日期:2009-12-01 00:00:00

  • Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells.

    abstract::Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5353

    authors: He Y,Huang H,Farischon C,Li D,Du Z,Zhang K,Zheng X,Goodin S

    更新日期:2017-02-01 00:00:00

  • Anti-hepatoma activities of ethyl acetate extract from Ampelopsis sinica root.

    abstract::Ampelopsis sinica root (ASR) is a known hepatoprotective folk traditional Chinese medicine. The anti‑hepatoma activity of ethyl acetate extract from A. sinica root (ASRE) in vitro and in vivo and its possible mechanism were explored. This study was designed to investigate cytotoxicity by MTT assay, induction of apopto...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5504

    authors: Wang JZ,Huang BS,Cao Y,Chen KL,Li J

    更新日期:2017-04-01 00:00:00

  • Downregulation of survivin expression and elevation of caspase-3 activity involved in pitavastatin-induced HepG 2 cell apoptosis.

    abstract::The aim of the present study was to research the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by pitavastatin. HepG 2 cells were treated with increasing doses of pitavastatin or with mevalonic acid for 48 h. The proliferation of cells was detected with WST-8. The morphology of the nucleus was o...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Wang J,Xu Z,Zhang M

    更新日期:2007-08-01 00:00:00

  • Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer.

    abstract::The high affinity nerve growth factor (NGF) NGF receptor, p75NTR, is a member of the tumor necrosis factor (TNF) receptor superfamily that shares a conserved intracellular death domain capable of inducing apoptosis and suppressing growth in prostate epithelial cells. Expression of this receptor is lost as prostate can...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4832

    authors: Gravina GL,Marampon F,Sanità P,Mancini A,Colapietro A,Scarsella L,Jitariuc A,Biordi L,Ficorella C,Festuccia C

    更新日期:2016-07-01 00:00:00

  • Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation.

    abstract::The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells b...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5587

    authors: Yasui H,Ohnishi Y,Nakajima M,Nozaki M

    更新日期:2017-06-01 00:00:00

  • MYC promotes the development of papillary thyroid carcinoma by inhibiting the expression of lncRNA PAX8‑AS1:28.

    abstract::As a common malignancy of the endocrine system, papillary thyroid carcinoma (PTC) seriously affects the quality of life of patients. lncRNA PAX8‑AS1:28, or lnc‑PSD4‑1:14 has been reported to be abnormally expressed in PTC. However, the function of PAX8‑AS1:28 in PTC is still unknown. Therefore, the present study aimed...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.6996

    authors: Zhang Y,Li F,Chen J

    更新日期:2019-04-01 00:00:00

  • Tiron, a ROS scavenger, protects human lung cancer Calu-6 cells against antimycin A-induced cell death.

    abstract::Antimycin A (AMA) inhibits the mitochondrial electron transport between cytochromes b and c. However, the relationship between AMA and lung cancer cells is poorly understood. In this study, we investigated the involvement of reactive oxygen species (ROS) and glutathione (GSH) in AMA-treated lung cancer Calu-6 cell dea...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Han YH,Park WH

    更新日期:2009-01-01 00:00:00

  • Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression.

    abstract::Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endot...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4000

    authors: Kim JH,Kim HJ,Kim JK,Ahn EK,Ko HJ,Cho YR,Lee SJ,Bae GU,Kim YK,Park JW,Oh JS,Seo DW

    更新日期:2015-07-01 00:00:00

  • Gene expression profiling of HL-60 cells following knockdown of nucleostemin using DNA microarrays.

    abstract::Nucleostemin (NS) plays an important role in tumorigenesis and progression. Most studies consider that NS plays its role through combining with p53 and inhibiting it, however our previous studies revealed that NS could also function without the existence of p53. To date, few studies have focused on the p53-independent...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3240

    authors: Sun X,Jia Y,Wei Y,Liu S,Yue B

    更新日期:2014-08-01 00:00:00

  • Hyperthermia inhibits the proliferation and invasive ability of mouse malignant melanoma through TGF-β(1).

    abstract::The degradation of basement membranes by tumor cells involves secretion and activation of proteinases, such as the matrix metalloproteinases (MMPs), and results from an imbalance between their inhibitors and activators that are controlled by various growth factors or cytokines, among which TGF-β(1) may be the most int...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2128

    authors: Jin H,Xie X,Hu B,Gao F,Zhou J,Zhang Y,Du L,Wang X,Zhao L,Zhang X,Shen L,Liao Y,Tang J

    更新日期:2013-02-01 00:00:00

  • Inhibition of proliferation, sprouting, tube formation and Tie2 signaling of lymphatic endothelial cells by the histone deacetylase inhibitor SAHA.

    abstract::Histone deacetylase (HDAC) inhibitors exert potent inhibitory effects on various types of human cancer. The pioneer drug suberoylanilide hydroxamic acid (SAHA) is currently used in the clinic for cancer treatment. However, the effect of SAHA on tumor lymphangiogenesis is unclear. We recently showed that SAHA suppresse...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2523

    authors: Cheng HT,Hung WC

    更新日期:2013-08-01 00:00:00

  • Perillyl alcohol causes G1 arrest through p15(INK4b) and p21(WAF1/Cip1) induction.

    abstract::The monoterpene perillyl alcohol (POH) is a naturally occurring compound derived from citrus fruits, mint and herbs. It exhibited chemotherapeutic potential against various malignant tumors in preclinical models and is currently being tested in clinical trials in patients with refractory advanced cancers. POH inhibits...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2167

    authors: Koyama M,Sowa Y,Hitomi T,Iizumi Y,Watanabe M,Taniguchi T,Ichikawa M,Sakai T

    更新日期:2013-02-01 00:00:00

  • Microarray analysis reveals differentially expressed lncRNAs in benign epithelial ovarian cysts and normal ovaries.

    abstract::Recent studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in many types of human malignant cancers. However, the function of lncRNAs in benign tumors remains poorly understood. In the present study, to explored the potential roles of lncRNAs in benign epithelial ovarian cysts (BEOCs) which commonly...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5741

    authors: Liu X,Dai C,Jia G,Xu S,Fu Z,Xu J,Li Q,Ruan H,Xu P

    更新日期:2017-08-01 00:00:00

  • miR‑107‑5p promotes tumor proliferation and invasion by targeting estrogen receptor‑α in endometrial carcinoma.

    abstract::The aberrant expression of miR107‑5p is closely related to the development of several types of human cancers. However, the role of miR‑107‑5p in endometrial carcinoma (EC) has not been fully confirmed. In the present study, we aimed to explore the function of miR‑107‑5p in EC carcinogenesis. EC samples and normal endo...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6936

    authors: Bao W,Zhang Y,Li S,Fan Q,Qiu M,Wang Y,Li Y,Ji X,Yang Y,Sang Z,Xu W,Yang Y,Wu S,Zhu Y

    更新日期:2019-03-01 00:00:00

  • Combined use of PI3K and MEK inhibitors synergistically inhibits lung cancer with EGFR and KRAS mutations.

    abstract::EGFR and KRAS mutations are the two most common driver mutations in non-small cell lung cancer (NSCLC). Molecular target-based therapy using small molecules such as gefitinib has been used for inhibiting EGFR with good initial responses; however, drug resistance is common when using a mono-targeting strategy. At prese...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4770

    authors: Jiang ZB,Huang J,Xie C,Li X,Liu L,He J,Pan H,Huang L,Fan XX,Yao XJ,Xie Y,Li N,Liu L,He JX,Leung EL

    更新日期:2016-07-01 00:00:00

  • Differential expression of heat shock protein 27 in normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma.

    abstract::The aim of this study was to evaluate HSP27 expression in fetal, normal and inflamed oral mucosal epithelium and in oral premalignant epithelial lesions and in their ensuing invasive cancers. In developing human oral epithelia, immunoreactions for HSP27 were moderately observed in suprabasal keratinocytes of palate an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Leonardi R,Pannone G,Magro G,Kudo Y,Takata T,Lo Muzio L

    更新日期:2002-03-01 00:00:00

  • Hepatitis B virus X protein sensitizes HL-7702 cells to oxidative stress-induced apoptosis through modulation of the mitochondrial permeability transition pore.

    abstract::Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and cancer. Among the pathogenic factors of HBV, HBV X protein (HBx) is attracting increased attention. Although it is documented that HBx is a multifunctional regulator that modulates cell inflammation and apoptosis, the exact mechanism r...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5225

    authors: Gao WY,Li D,Cai DE,Huang XY,Zheng BY,Huang YH,Chen ZX,Wang XZ

    更新日期:2017-01-01 00:00:00

  • A new curcumin analogue exhibits enhanced antitumor activity in nasopharyngeal carcinoma.

    abstract::The aim of the present study was to evaluate the antitumor effects of the curcumin analogue GL63 on radioresistant nasopharyngeal carcinoma (NPC) CNE2R cells and parental CNE2 cells. The cell viability and proliferation of NPC cells were detected by MTT assay and colony formation assay. The suppressive effect on tumor...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2457

    authors: Pan Y,Xiao J,Liang G,Wang M,Wang D,Wang S,Yang H

    更新日期:2013-07-01 00:00:00

  • Morusin suppresses A549 cell migration and induces cell apoptosis by downregulating the expression of COX‑2 and VEGF genes.

    abstract::The present study aimed to examine the inhibitory effects of morusin on the human lung cancer cell line A549. Various doses of morusin were applied to A549 cells and the effects were assessed by wound‑healing and MTT assays, flow cytometry analysis of apoptosis, a mitochondrial membrane potential assay and RT‑PCR. The...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6431

    authors: Yin XL,Lv Y,Wang S,Zhang YQ

    更新日期:2018-07-01 00:00:00

  • Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro.

    abstract::Previous studies have demonstrated the tremendous tropism of mesenchymal stem cells (MSCs) for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, the mechanisms underlying the tropism of MSCs for gliomas remain poorly defined. It has been ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000796

    authors: Xu F,Shi J,Yu B,Ni W,Wu X,Gu Z

    更新日期:2010-06-01 00:00:00

  • Mapping of the critical region of mitogene-inducible gene-6 for NF-kappaB activation.

    abstract::Mitogene-inducible gene-6 (Mig-6) is involved in the intracellular signaling pathway as an adaptor molecule. Mig-6 expression is rapidly induced upon various kinds of mitogenic and stressful stimulations. We previously demonstrated that Mig-6 expression is induced by activated Ki-ras in human colon cancer cells and th...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Mabuchi R,Sasazuki T,Shirasawa S

    更新日期:2005-03-01 00:00:00

  • SPARC expression is negatively correlated with clinicopathological factors of gastric cancer and inhibits malignancy of gastric cancer cells.

    abstract::Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein which plays multiple roles in different types of cancer. Our previous study showed that SPARC overexpression inhibited the growth and angiogenesis of tumors, and reduced expression of vascular endothelial growth factor (VEGF). However, the relation...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3118

    authors: Zhang J,Wang P,Zhu J,Wang W,Yin J,Zhang C,Chen Z,Sun L,Wan Y,Wang X,Chen G,Liu Y

    更新日期:2014-05-01 00:00:00

  • The novel herbal cocktail MA128 suppresses tumor growth and the metastatic potential of highly malignant tumor cells.

    abstract::MA128, a novel herbal medicine, was previously identified and its effectiveness in the treatment of asthma and atopic dermatitis (AD) was demonstrated. In particular, post-inflammatory hyperpigmentation (PIH) in AD mice was improved by treatment with MA128. In addition, MA128 exhibited anti-melanogenic activity by inh...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4018

    authors: Kim A,Im M,Yim NH,Hwang YH,Yang HJ,Ma JY

    更新日期:2015-08-01 00:00:00

  • MicroRNA‑203a‑3p is a candidate tumor suppressor that targets thrombospondin 2 in colorectal carcinoma.

    abstract::The aim of the present study was to investigate the role of miR‑203a‑3p in colorectal cancer (CRC) and identify the target gene of microRNA (miR)‑203a‑3p. A total of 59 sets of cancer tissues and corresponding adjacent non‑tumor tissues were collected from CRC patients (aged 31‑78 years) between October 2016 and May 2...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7310

    authors: Qian Z,Gong L,Mou Y,Han Y,Zheng S

    更新日期:2019-11-01 00:00:00

  • Potential role of Notch1 signaling pathway in laryngeal squamous cell carcinoma cell line Hep-2 involving proliferation inhibition, cell cycle arrest, cell apoptosis, and cell migration.

    abstract::Head and neck cancer is the sixth most common cancer worldwide and laryngeal cancer represents the largest subgroup. However, the molecular mechanism underlying its malignant behavior and progression is not clarified. Accumulating evidence has shown that Notch1 signaling pathway plays a central role in carcinogenesis,...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000504

    authors: Jiao J,Qin Z,Li S,Liu H,Lu Z

    更新日期:2009-10-01 00:00:00

  • Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells.

    abstract::The mammalian target of rapamycin (mTOR) is a key kinase acting downstream of growth factor receptor PI3K and AKT signaling, leading to processes resulting in increased cell size and proliferation through translation control. Rapamycin, a specific inhibitor of mTOR, results predomin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1855

    authors: Miyake N,Chikumi H,Takata M,Nakamoto M,Igishi T,Shimizu E

    更新日期:2012-09-01 00:00:00

  • Elevated L1CAM expression in precursor lesions and primary and metastastic tissues of pancreatic ductal adenocarcinoma.

    abstract::The promigratory molecule L1CAM is overexpressed in various tumors, often representing an unfavorable prognostic marker. Recently, we identified L1CAM expression in pancreatic ductal adenocarcinoma (PDAC) cells accounting for chemoresistance and increased cell migration. Thus, the present study aims at further elucida...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2010.909

    authors: Bergmann F,Wandschneider F,Sipos B,Moldenhauer G,Schniewind B,Welsch T,Schirrmacher P,Klöppel G,Altevogt P,Schäfer H,Sebens Müerköster S

    更新日期:2010-10-01 00:00:00